Antibody landscape of C57BL/6 mice cured of B78 melanoma via a combined radiation and immunocytokine immunotherapy regimen

Sera of immune mice that were previously cured of their melanoma through a combined radiation and immunocytokine immunotherapy regimen consisting of 12 Gy of external beam radiation and the intratumoral administration of an immunocytokine (anti-GD2 mAb coupled to IL-2) with long-term immunological memory showed strong antibody-binding against melanoma tumor cell lines via flow cytometric analysis. Using a high-density whole-proteome peptide array (of 6.090.593 unique peptides), we assessed potential protein-targets for antibodies found in immune sera. Sera from 6 of these cured mice were analyzed with this high-density, whole-proteome peptide array to determine specific antibody-binding sites and their linear peptide sequence. We identified thousands of peptides that were targeted by these 6 mice and exhibited strong antibody binding only by immune (after successful cure and rechallenge), not naïve (before tumor implantation) sera and developed a robust method to detect these differentially targeted peptides. Confirmatory studies were done to validate these results using 2 separate systems, a peptide ELISA and a smaller scale peptide array utilizing a slightly different technology. To the best of our knowledge, this is the first study of the full set of germline encoded linear peptide-based proteome epitopes that are recognized by immune sera from mice cured of cancer via radio-immunotherapy. We furthermore found that although the generation of B-cell repertoire in immune development is vastly variable, and numerous epitopes are identified uniquely by immune serum from each of these 6 immune mice evaluated, there are still several epitopes and proteins that are commonly recognized by at least half of the mice studied. This suggests that every mouse has a unique set of antibodies produced in response to the curative therapy, creating an individual “fingerprint.” Additionally, certain epitopes and proteins stand out as more immunogenic, as they are recognized by multiple mice in the immune group

Cognitive Reserve and the Prevention of Dementia: the Role of Physical and Cognitive Activities

Purpose of Review: The article discusses the two most significant modifiable risk factors for dementia, namely, physical inactivity and lack of stimulating cognitive activity, and their effects on developing cognitive reserve. Recent Findings: Both of these leisure-time activities were associated with significant reductions in the risk of dementia in longitudinal studies. In addition, physical activity, particularly aerobic exercise, is associated with less age-related gray and white matter loss and with less neurotoxic factors. On the other hand, cognitive training studies suggest that training for executive functions (e.g., working memory) improves prefrontal network efficiency, which provides support to brain functioning in the face of cognitive decline. Summary: While physical activity preserves neuronal structural integrity and brain volume (hardware), cognitive activity strengthens the functioning and plasticity of neural circuits (software), thus supporting cognitive reserve in different ways. Future research should examine whether lifestyle interventions incorporating these two domains can reduce incident dementia

Increasing energy flux to maintain diet-induced weight loss

Long-term maintenance of weight loss requires sustained energy balance at the reduced body weight. This could be attained by coupling low total daily energy intake (TDEI) with low total daily energy expenditure (TDEE; low energy flux), or by pairing high TDEI with high TDEE (high energy flux). Within an environment characterized by high energy dense food and a lack of need for movement, it may be particularly difficult for weight-reduced individuals to maintain energy balance in a low flux state. Most of these individuals will increase body mass due to an inability to sustain the necessary level of food restriction. This increase in TDEI may lead to the re-establishment of high energy flux at or near the original body weight. We propose that following weight loss, increasing physical activity can effectively re-establish a state of high energy flux without significant weight regain. Although the effect of extremely high levels of physical activity on TDEE may be constrained by compensatory reductions in non-activity energy expenditure, moderate increases following weight loss may elevate energy flux and encourage physiological adaptations favorable to weight loss maintenance, including better appetite regulation. It may be time to recognize that few individuals are able to re-establish energy balance at a lower body weight without permanent increases in physical activity. Accordingly, there is an urgent need for more research to better understand the role of energy flux in long-term weight maintenance

Splenectomy Increases Mortality in Murine Trypanosoma cruzi Infection

The spleen is a secondary lymphoid organ that harbours a variety of cells such as T and B lymphocytes and antigen-presenting cells important to immune response development. In this study, we evaluated the impact of spleen removal in the immune response to experimental Trypanosoma cruzi infection. C57BL/6 mice were infected with Y strain of the parasite and infection was followed daily. Mice that underwent splenectomy had fewer parasites in peripheral blood at the peak of infection; however, mortality was increased. Histological analysis of heart and liver tissues revealed an increased number of parasites and inflammatory infiltrates at these sites. Spleen removal was associated with reduction in IFN-γ and TNF-α production during infection as well as with a decrease in specific antibody secretion. Haematological disorders were also detected. Splenectomized mice exhibited severe anaemia and decreased bone marrow cell numbers. Our results indicate that spleen integrity is critical in T. cruzi infection for the immune response against the parasite, as well as for the control of bone marrow haematological function

Effect of Race and Marital Status on Mothers’ Observed Parenting and Adolescent Adjustment in Youth With Type 1 Diabetes

Objective To examine demographic differences in parenting behaviors and adjustment in youth with type 1 diabetes. Methods Adolescents’ psychosocial adjustment was assessed via self-reports and parent reports, and clinical data were obtained from adolescents’ medical records. Mother–adolescent dyads (N = 93) engaged in a videotaped discussion task, which was coded for observed parenting behaviors. Results Single and non-White mothers exhibited significantly more overinvolved and less collaborative parenting behaviors. Higher levels of overinvolved parenting and lower levels of collaborative parenting were associated with poorer adolescent adjustment (i.e., higher levels of externalizing problems). Observed parenting was not significantly associated with glycemic control. There was an indirect effect of marital status and race/ethnicity on externalizing behaviors through parenting. Conclusions The current study highlights parenting as a potential target for interventions, especially in single and minority mothers, to improve adjustment in this population